OBJECTIVES: PEGylated interferon beta-1a (PEG-IFN beta-1a) is being developed for the treatment of relapsing-remitting multiple sclerosis (MS). PEGylated drugs are commonly used in other therapeutic areas, including oncology and hepatitis, but none are currently approved for MS. This study was conducted to gain a better understanding of the published humanistic and patient quality of life benefits of PEGylated drugs currently available for the treatment of other diseases. METHODS: A comprehensive search of medical literature published between 1985 and 2010 was conducted using PubMed/MEDLINE and supplemental searches. Reviewed references were prospective or retrospective studies reporting the tolerability, health-related quality of life (HRQOL), convenience, compliance, and patient preferences associated with PEGylated drugs. Only studies comparing PEGylated drugs to their corresponding non-PEGylated counterparts in the same therapeutic area were included in the analysis.  RESULTS: Fifty-nine articles and 12 conference abstracts were reviewed. Eleven PEGylated drugs were identified, 6 of which had corresponding non-PEGylated counterparts. All 6 of these PEGylated drugs were administered less frequently than their non-PEGylated counterparts yet exhibited similar or greater efficacy, along with greater patient convenience. PEGylated drugs were generally tolerated as well as or better than their non-PEGylated counterparts. In HRQOL studies, patients who received PEGylated drugs reported better HRQOL than those receiving non-PEGylated drugs across a broad spectrum of domains, as well as in global HRQOL scores. For studies measuring quality-adjusted life-years (QALYs), PEGylated drugs were reported to produce more QALYs than their non-PEGylated counterparts. While few studies have evaluated patient medication compliance and patient preference/satisfaction, the published results of these studies also favor PEGylated drugs.  CONCLUSIONS: PEGylated drugs are reported to be tolerated at least as well as their non-PEGylated counterparts and to be associated with higher HRQOL and greater patient preference/satisfaction, convenience, and compliance. PEG-IFN beta-1a may offer similar benefits to patients with MS.